The HTLV-1 viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape.
Basic-Leucine Zipper Transcription Factors
/ metabolism
Gene Products, tax
/ metabolism
HEK293 Cells
HTLV-I Infections
/ etiology
Human T-lymphotropic virus 1
Humans
Jurkat Cells
Leukemia-Lymphoma, Adult T-Cell
/ virology
RNA Splicing
RNA, Messenger
Retroviridae Proteins
/ metabolism
Splicing Factor U2AF
/ metabolism
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
23
03
2021
accepted:
27
08
2021
revised:
30
09
2021
pubmed:
21
9
2021
medline:
25
11
2021
entrez:
20
9
2021
Statut:
epublish
Résumé
Viral infections are known to hijack the transcription and translation of the host cell. However, the extent to which viral proteins coordinate these perturbations remains unclear. Here we used a model system, the human T-cell leukemia virus type 1 (HTLV-1), and systematically analyzed the transcriptome and interactome of key effectors oncoviral proteins Tax and HBZ. We showed that Tax and HBZ target distinct but also common transcription factors. Unexpectedly, we also uncovered a large set of interactions with RNA-binding proteins, including the U2 auxiliary factor large subunit (U2AF2), a key cellular regulator of pre-mRNA splicing. We discovered that Tax and HBZ perturb the splicing landscape by altering cassette exons in opposing manners, with Tax inducing exon inclusion while HBZ induces exon exclusion. Among Tax- and HBZ-dependent splicing changes, we identify events that are also altered in Adult T cell leukemia/lymphoma (ATLL) samples from two independent patient cohorts, and in well-known cancer census genes. Our interactome mapping approach, applicable to other viral oncogenes, has identified spliceosome perturbation as a novel mechanism coordinated by Tax and HBZ to reprogram the transcriptome.
Identifiants
pubmed: 34543356
doi: 10.1371/journal.ppat.1009919
pii: PPATHOGENS-D-21-00613
pmc: PMC8483338
doi:
Substances chimiques
Basic-Leucine Zipper Transcription Factors
0
Gene Products, tax
0
HBZ protein, human T-cell leukemia virus type I
0
RNA, Messenger
0
Retroviridae Proteins
0
Splicing Factor U2AF
0
U2AF2 protein, human
0
tax protein, Human T-lymphotrophic virus 1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009919Subventions
Organisme : NHGRI NIH HHS
ID : P50 HG004233
Pays : United States
Organisme : NHGRI NIH HHS
ID : U41 HG001715
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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